In Vivo Ocular Angiogenesis Assay

体内眼部血管生成测定

• 批准号: 7687368
• 负责人: WEN L SENG
• 金额: $ 40.82万
• 依托单位: PHYLONIX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687368
• 关键词: Adult; Affect; Age related macular degeneration; Angiogenesis Inhibitors; Animal Model; Animal Testing; Antibodies; Biological Assay; Biological Products; Blindness; Blood Vessels; Caliber; Clinical Services; Clinical Trials; Contracts; Cornea; Corneal Neovascularization; Deposition; Development; Developmental Delay Disorders; Diabetic Retinopathy; Disease; Dose; Embryo; Employee Strikes; Enzymes; Evaluation; Extravasation; Eye; Fertilization; Germany; Government; Hour; Human; Immunohistochemistry; Infection; Injury; Label; Lead; Length; Libraries; Link; Mammals; Measurement; Mediating; Modeling; Newborn Infant; Operative Surgical Procedures; Ophthalmic examination and evaluation; Oxygen; Performance; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Preclinical Drug Evaluation; Premature Infant; Process; Provider; Rattus; Reader; Reading; Research; Retina; Retinal Detachment; Retinopathy of Prematurity; Rivers; Services; Signal Transduction; Staining method; Stains; Supplementation; Time; Vascular Diseases; Vascular Endothelial Growth Factors; Vision; Visual; Zebrafish; angiogenesis; base; collagenase; drug candidate; drug testing; improved; in vivo; neovascularization; novel therapeutics; ocular angiogenesis; ocular neovascularization; postnatal; programs; research clinical testing; research study; therapeutic development; tumor

DESCRIPTION (provided by applicant): Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the two leading causes of blindness in adults in the industrialized world. Both conditions involve vascular abnormalities, proliferation and leakage of new blood vessels. Retinopathy of prematurity (ROP) is a major cause of newborn blindness in premature infants maintained by oxygen supplementation during the postnatal period. This disease involves intense neovascularization of the retina and leads to retinal detachment. Another cause of blindness is corneal neovascularization, which often results from injury and infection in the cornea. Current mammalian models for ocular neovascularization require lengthy, tedious surgical manipulation and do not always result in improved vision; an alternative rapid, less invasive animal model for studying the process of ocular neovascularization and assessing drug effects will facilitate identification of new therapeutics. Using zebra fish, Phase I research developed a micro plate assay for quantifying effects of angiogenic compounds on ocular neovascularization. Phase II research will perform a pilot screen of available commercially compounds and confirm positive "hits" identified in conventional animal models. Phase II research will further validate the utility of the zebra fish model for screening drugs for treating debilitating diseases involving neovascularization. By providing a quantitative in vivo assay for assessing drug effects on ocular neovascularization, the proposed zebra fish assay will facilitate development of therapeutic drugs for treating debilitating diseases involving neovascularization.

描述(申请人提供)：糖尿病视网膜病变(DR)和年龄相关性黄斑变性(AMD)是工业化世界成年人失明的两个主要原因。这两种情况都涉及血管异常、新血管的增殖和渗漏。早产儿视网膜病变(ROP)是早产儿出生后通过补充氧气维持新生儿失明的主要原因。这种疾病涉及强烈的视网膜新生血管，并导致视网膜脱离。失明的另一个原因是角膜新生血管，这通常是由于角膜损伤和感染造成的。目前的眼部新生血管的哺乳动物模型需要长时间、繁琐的手术操作，而且并不总是能改善视力；另一种快速、侵入性较小的动物模型用于研究眼部新生血管的过程和评估药物效果，将有助于识别新的治疗方法。利用斑马鱼，第一阶段研究开发了一种微型平板分析方法，用于量化新生血管化合物对眼部新生血管的影响。第二阶段的研究将对可用的商业化合物进行试点筛选，并确认在传统动物模型中确定的阳性“命中”。第二阶段的研究将进一步验证斑马鱼模型用于筛选治疗涉及新生血管的衰弱疾病的药物的实用性。通过提供一种用于评估药物对眼部新生血管的影响的体内定量检测方法，拟议的斑马鱼检测方法将促进治疗涉及新生血管的衰弱疾病的治疗药物的开发。